An Open-Label, Randomized, Multicenter Phase 3 Study Investigating the Efficacy and Safety of BGB-43395 Plus Letrozole Versus CDK4/6 Inhibitors (Abemaciclib, Palbociclib, Ribociclib) Plus Letrozole in Patients With Advanced or Metastatic HR+/HER2- Breast Cancer Who Have Not Received Prior Systemic Anticancer Treatment for Advanced or Metastatic Disease
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- BeOne Medicines
- Enrollment
- 1,056
- Primary Endpoint
- Progression-Free Survival (PFS) Determined by Blinded Independent Central Review (BICR)
Overview
Brief Summary
The purpose of this study is to investigate the efficacy and safety of BGB-43395 in combination with letrozole compared with investigator's choice of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in combination with letrozole in patients with advanced or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) who have not received prior systemic treatment for advanced or metastatic disease.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the informed consent.
- •Participants with histologically confirmed locally advanced or metastatic HR+ HER2- breast cancer.
- •Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤
- •Adequate organ function.
Exclusion Criteria
- •Participants who have received prior systemic treatment in the advanced or metastatic setting.
- •Participants who have received prior treatment with any selective cyclin-dependent kinase 4 (CDK4) or cyclin-dependent kinase 2 (CDK2) targeting agent, or any other investigational anticancer drug in any disease setting, except for prior investigational or approved SERDs in the adjuvant setting, provided that disease recurrence occurred more than 12 months after the last dose of endocrine-based therapy.
- •Participants with active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- •Note: Other protocol-defined inclusion/exclusion criteria may apply.
Arms & Interventions
Arm B: Cyclin-Dependent Kinase 4/6 Inhibitor + Letrozole
Participants will receive either abemaciclib, palbociclib, or ribociclib based on the Investigator's choice in combination with letrozole.
Intervention: Palbociclib (Drug)
Arm A: BGB-43395 + Letrozole
Participants will receive BGB-43395 in combination with letrozole.
Intervention: BGB-43395 (Drug)
Arm A: BGB-43395 + Letrozole
Participants will receive BGB-43395 in combination with letrozole.
Intervention: Letrozole (Drug)
Arm B: Cyclin-Dependent Kinase 4/6 Inhibitor + Letrozole
Participants will receive either abemaciclib, palbociclib, or ribociclib based on the Investigator's choice in combination with letrozole.
Intervention: Letrozole (Drug)
Arm B: Cyclin-Dependent Kinase 4/6 Inhibitor + Letrozole
Participants will receive either abemaciclib, palbociclib, or ribociclib based on the Investigator's choice in combination with letrozole.
Intervention: Abemaciclib (Drug)
Arm B: Cyclin-Dependent Kinase 4/6 Inhibitor + Letrozole
Participants will receive either abemaciclib, palbociclib, or ribociclib based on the Investigator's choice in combination with letrozole.
Intervention: Ribociclib (Drug)
Outcomes
Primary Outcomes
Progression-Free Survival (PFS) Determined by Blinded Independent Central Review (BICR)
Time Frame: Up to approximately 4 years
PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Secondary Outcomes
- Progression-Free Survival 2 (PFS2)(Up to approximately 4 years)
- Overall Survival (OS)(Up to approximately 11 years)
- Overall Response Rate (ORR)(Up to approximately 4 years)
- Duration of Response (DOR)(Up to approximately 4 years)
- PFS Determined by Investigator(Up to approximately 4 years)
- Clinical Benefit Rate (CBR)(Up to approximately 4 years)
- Time to Response (TTR)(Up to approximately 4 years)
- Number of Participants with Adverse Events (AEs)(From first dose of study drug up to 30 days after last dose, up to approximately 11 years)
- Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC)-Item Library (IL)454.(Baseline and up to approximately 4 years)